A method for identifying neoantigens through isolation of circulating tumor cells using apheresis among patients with advanced-stage cancer
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Le résumé fourni par la source
Background Immune checkpoint inhibitors show limited efficacy in tumors with low tumor mutational burden, partly due to insufficient neoantigen presentation. Methods We developed a novel approach for neoantigen identification using circulating tumor cells (CTCs) isolated via leukapheresis and flow cytometry. Peripheral blood mononuclear cells (PBMCs) were collected from 11 stage IV cancer patients and 2 healthy volunteers. CTCs were enriched by depleting CD45+ hematopoietic cells and selecting CD45−Vimentin+ cells, which were confirmed cytologically to contain malignant cells. Hematopoietic lineage analysis showed that over 50% of the CTC fraction consisted of non-hematopoietic cells. DNA extracted from both the CTC and normal hematopoietic fractions underwent exome sequencing. Neoantigens were identified using the Ancer® bioinformatics platform. Results In representative patients with gastric and salivary gland cancers, 94,636 and 46,423 CTCs were isolated, respectively. DNA yields were sufficient for exome sequencing without amplification or extensive cell culture. A total of 102 (patient with gastric cancer) and 108 (patient with salivary gland cancer) neoantigens were identified in each subject, including high-ranking T-cell epitopes derived from single nucleotide variants and frameshift mutations. According to the same procedures we could successfully identify a large number of neoantigens from the CTCs of all stage IV cancer patients. This confirms the feasibility of identifying individual patient-specific neoantigens from CTCs without requiring tumor biopsies. Conclusions This is the first study to demonstrate successful neoantigen identification using non-amplified CTCs isolated by apheresis and flow cytometry. The approach provides a minimally invasive, scalable alternative for neoantigen discovery and may better capture tumor heterogeneity compared to single-site biopsies. This method holds promise for enabling rapid, personalized immunotherapy strategies, including peptide vaccines, dendritic cell vaccines, and mRNA-based treatments.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A method for identifying neoantigens through isolation of circulating tumor cells using apheresis among patients with advanced-stage cancer
- Date Crossref
- 11/07/2025
- Éditeur
- Frontiers Media SA
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Fujita Health University pays non établi dans la noticeUniversité ou école supérieure
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Tokyo Medical University Ibaraki Medical Center Department of Medicine pays non établi dans la noticeÉtablissement de santé
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Musashino University pays non établi dans la noticeUniversité ou école supérieure
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EpiVax (United States) pays non établi dans la noticeEntreprise
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Hijikata Clinic pays non établi dans la noticeÉtablissement de santé
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Biomedica Solution Inc. pays non établi dans la noticeEntreprise
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University of Musashino Research Institute of Pharmaceutical Sciences pays non établi dans la noticeUniversité ou école supérieure
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EpiVax Inc. pays non établi dans la noticeEntreprise
Fujita Health University, Department of Medicine — Tokyo Medical University Ibaraki Medical Center et Musashino University, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.